Dementia

Question 1

Definition of dementia

Answer 1

Significant cognitive impairment in at least one area
Acquired impairment - significant decline from baseline
Cognitive deficits must interfere with ADLs
Exclude other causes eg delirium

Question 2

Areas where cognitive impairment can occur

Answer 2

Learning and memory
Language
Executive functioning
Complex attention
Perceptual motor function
Social cognition

Question 3

What is mild cognitive impairment

Answer 3

Impaired cognition without affecting function

Question 4

How many people progress from mild cognitive impairment to dementia

Answer 4

10-15% per year

Question 5

Predictors for conversion to dementia from mild cognitive impairment

Answer 5

Age
Hypertension
Lower education
Verbal and executive dysfunction
Depression
Hippocampal size
Apo E4
MRI changes
CSF - elevated Tau

Question 6

Most common cause of dementia

Answer 6

Alzheimers disease

Question 7

Pathogenesis of Alzheimers disease

Answer 7

Neuritic plaques containing amyloid beta form outside cells and accumulate in blood vessels
Neurofibrillary tangles of tau protein form inside cells and impair axon transport
Spread from medial temporal lobe to temporal neocortex to other parts of cortex

Question 8

Genetics of Alzheimers

Answer 8

Apo E gene

• found on chromosome 19
• if have one allele - increased risk of AD by 2-3x
• if have two alleles - increased risk of AD by 8-12x

Familial AD (early onset)

• APP gene on chromosome 21, implicated in Downs syndrome dementia
• Presenilin 1 and 2 mutations - can’t cleave amyloid

Question 9

Risk factors for Alzheimers

Answer 9

ApoE4 allele
Age (strongest risk factor)
Family history
Female
Type 2 diabetes
Obesity
Increased homocysteine, cholesterol and blood pressure
Less physical activity

Question 10

Clinical features of Alzheimers

Answer 10

Episodic memory loss
Language - anomia, empty speech, logopenic aphasia
Visuospatial deficit
Executive function
Disorientation, agraphia, acalculia
Apraxia - difficulty performing learnt tasks

Non cognitive

• depression
• apathy
• delusions - Capgras
• olfactory dysfunction
• agitation, paranoia

Question 11

Diagnosis of Alzheimers

Answer 11

Involve 2 domains of cognitive impairment
MRI - hippocampal atrophy, parietal atrophy, ventricular enlargement
FDG-PET - parieto-temporal hypometabolism
C-PIB-PET - accumulation of cortical fibrillar amyloid
CSF - low amyloid beta levels, high level of phosphorylated Tau

Question 12

Pharmacological options for Alzheimers

Answer 12

Acetylcholinesterase inhibitors (Donepezil) - increase levels of acetylcholine, used in mild-moderate AD

NMDA receptor antagonist (Memantine) - reduces excitotoxicity of glutamate on hippocampus, benefit in moderate-severe AD

Question 13

Side effects of acetylcholinesterase inhibitors

Answer 13

Diarrhoea
Nausea
vomiting
Cramps
CI in asthma, peptic ulcer disease, conduction defects

Question 14

Side effects of memantine

Answer 14

Dizziness
Confusion
Drowsiness